Potential glycerol production inducers in <i>Saccharomyces cerevisiae</i> identified by <i>in silico</i> approaches

Glycerol has widespread applications in food, pharmaceuticals, cosmetics, and various industrial sectors. While its chemical production entails purification challenges, microbial fermentation, particularly employing <i>Saccharomyces cerevisiae</i>, presents a promising alternative. This study used computational techniques to identify potential inhibitors of <i>S. cerevisiae</i> alcohol dehydrogenase (ADH) to enhance glycerol production. High-throughput virtual screening of 190,000 natural compounds from the ZINC database revealed 116 potential ADH inhibitors. Based on <i>in silico</i> toxicity screening, six compounds, including a quinoline derivative, ZINC000005398892, imidazopyridoindol analog (ZINC000008918046), and four hydroxyoctahydroisoquinolin-chromenone derivatives, ZINC000002111805, ZINC000015954814, ZINC000104739723, and ZINC000002111093, were predicted to be non-mutagenic and non-carcinogenic. Molecular dynamics (MD) simulation studies confirmed the stability of these compounds during 50 ns. ZINC000002111093 was found to be the best compound in this regard. Overall, the selected natural compounds could be potential candidates to direct the metabolic pathway in <i>S. cerevisiae</i> toward enhanced production of glycerol instead of alcohol. Experimental studies can confirm these findings.